Xiling
Yang
a,
Yun
Li
a,
Peisen
Zhang
*bc,
Lingfei
Guo
a,
Xiaoqi
Li
a,
Yiyang
Shu
a,
Kuiyu
Jiang
a,
Yi
Hou
c,
Lihong
Jing
*b and
Mingxia
Jiao
*a
aKey Laboratory of Optic-Electric Sensing and Analytical Chemistry for Life Science, MOE, College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Zhengzhou Road 53, Qingdao 266042, China. E-mail: jiaomingxia@qust.edu.cn
bKey Laboratory of Colloid, Interface and Chemical Thermodynamics, Institute of Chemistry, Chinese Academy of Sciences, Bei Yi Jie 2, Zhong Guan Cun, Beijing 100190, China. E-mail: zhangps@iccas.ac.cn; jinglh@iccas.ac.cn
cCollege of Life Science and Technology, Beijing University of Chemical Technology, Beijing, 10029, China
First published on 19th July 2023
Advanced nanoplatforms equipped with different functional moieties for theranostics hold appealing promise for reshaping precision medicine. The reliable construction of an individual nanomaterial with intrinsic near-infrared (NIR) photofunction and magnetic domains is much desired but largely unexplored in a direct aqueous synthesis system. Herein, we develop an aqueous phase synthetic strategy for Mn2+ doping of ZnS shell grown on Zn–Cu–In–Se core quantum dots (ZCISe@ZnS:Mn QDs), providing the optimal NIR fluorescence quantum efficiency of up to 18.9% and meanwhile efficiently introducing paramagnetic domains. The relaxometric properties of the water-soluble Mn-doped QDs make them desirable for both the longitudinal and transverse (T1 and T2) magnetic resonance (MR) contrast enhancement due to the shell lattice-doped Mn2+ ions with slow tumbling rates and favoured spin-proton dipolar interactions with surrounding water molecules. Surprisingly, the incorporation of Mn2+ ions into the shell is found to significantly enhance the production of reactive oxygen species (ROS) by combining both the chemodynamic and photodynamic processes upon NIR light irradiation, showing great potential for efficient photo-assisted ablation of cancer cells. Furthermore, a broad-spectrum excitation range beneficial for bright NIR fluorescence imaging of breast cancer has been proven and offers high flexibility in the choice of incident light sources. Multiparametric MR imaging of the brain has also been successfully demonstrated in vivo.
Ternary I–III–VI semiconductor nanocrystals or quantum dots (QDs), such as copper indium selenide QDs, have become attractive alternatives to the more well-established Cd-, Pb-, or Hg-containing QDs for in vivo applications.7–12 Apart from their good biocompatibility due to the absence of highly toxic elements, their relatively narrow bulk band gaps allow the tuning of photoluminescence from the visible region all the way up to the near-infrared (NIR) spectral region,13–19 where penetration through biological tissue is favorable.20–24 In contrast to binary Cd-free QDs, ternary QDs show composition-dependent optical properties while maintaining similar particle sizes, which endows the QDs with analogous pharmacokinetic behaviors in vivo. As a consequence, ternary QDs with NIR emission have been intensively exploited for imaging in vivo.7,9,25,26 Unfortunately, the majority of I–III–VI QDs suffer from far lower photoluminescence quantum yields (PLQYs) compared with their binary counterparts,27,28 which goes against high sensitivity in terms of imaging. The low PLQY is largely due to the existence of abundant intrinsic defects in ternary QDs, including vacancies, antisite and interstitial defects related to non-radiative relaxation of photoexcited charge carriers.29,30 To solve the above problem, Zn alloying has been employed to improve the PLQY of I–III–VI QDs by reducing Cu+-related defects and restraining the non-radiative recombination.31 On the opposite side, the generated radicals or heat involved in nonradiative recombination pathways give us the opportunity to use them for photodynamic or photothermal therapy (PDT/PTT).32,33 For example, in a recent report Li et al. demonstrated the successful utilization of CuInSe2-based QDs for simultaneous PDT and PTT of breast cancer tumors.25
To endow optical imaging agents with complemental modality such as magnetic resonance imaging (MRI) to overcome their inherent limitation of spatial resolution,34,35 magnetic components are often chosen to be loaded into QDs by incorporating, chelating or heteroepitaxial growth.36–41 In these cases, the fluorescence of the QD core is easily deteriorated by the quenching effect of magnetic domains. In contrast, doping magnetic ions into a compatible semiconductor shell of host QDs can further reduce the negative impact of magnetic doping on the QD core, which is a promising way to produce reliable materials with intrinsic fluorescence and magnetism to address the challenge mentioned above.25,42 For example, Chetty et al. reported Mn2+/Gd3+ co-doped CuInS2–ZnS QDs for early diagnosis of subcutaneous melanoma through fluorescence, MR, and CT imaging.42 Apart from acting as an imaging modality, Mn2+ ions have been found to play an important role in treatment applications. For example, the Jiang group reported the importance of manganese in antitumor immune responses via cGAS–STING to improve the efficacy of immunotherapy.43 In another report, single-atom Mn on the surface of Ag2Te QDs was found by Huang et al. to exhibit catalytic activity for scavenging reactive oxygen species to alleviate neuroinflammation in the brain.23 The above research studies indicate that Mn2+ ions doped into multinary QDs may have undiscovered influences on the nonradiative recombination processes, which deserves further investigation to better reveal the functions of manganese doping.
Following our previous studies on the synthesis and bioapplication of ternary QDs,31,44–46 we herein report a green and mild method for preparing NIR-emitting manganese-doped Zn–Cu–In–Se-based QDs under aqueous conditions. Paramagnetic Mn2+ ions were chosen to be doped into a ZnS shell epitaxially grown on Zn–Cu–In–Se core QDs to further retain the high NIR PLQY. Mn2+ doping effects on both the optical and magnetic properties as well as the structure of QDs were systemically studied. Interestingly, the incorporation of Mn2+ ions into the shell of QDs was found to promote the photodynamic processes with the aid of light irradiation, to yield more reactive oxygen species for killing tumor cells. Furthermore, the biocompatible QDs with broad excitation and bright NIR fluorescence were successfully applied for multichannel imaging of breast cancer in vivo. Moreover, multiparametric MR imaging of the brain has also been successfully demonstrated in vivo.
All animal procedures reported here were performed in accordance with the Guidelines for Care and Use of Laboratory Animals of Peking University Health Science Center, and approved by the Peking University Institutional Animal Care and Use Committee. The assigned accreditation number of the investigator is LA2022284.
T 1-weighted imaging (T1WI), T2-weighted imaging (T2WI), T2*-weighted imaging (T2*WI), and susceptibility-weighted imaging (SWI) sequences were obtained before and after intracranial injection of ∼10 μL PBS solution of the QDs (0.122 mg Cu per kg). During the MRI experiments, the animals were anesthetized with 2% isoflurane in oxygen-mixed air via a facemask. The detailed parameters for these sequences were set as follows:
T 1WI: TR = 500 ms, TE = 5.24 ms, FoV = 22 × 22 mm, matrix = 191 × 191, and slice thickness = 0.5 mm;
T 2WI: TR = 3000 ms, TE = 40 ms, FoV = 22 × 22 mm, MTX = 191 × 191, and slice thickness = 0.5 mm;
T 2*WI: TR = 1479.31 ms, TE = 3.32 ms, FoV = 22 × 22 mm, MTX = 191 × 191, and slice thickness = 0.5 mm;
SWI: TR = 595.17 ms, TE = 7.9 ms, FoV = 22 × 22 mm, matrix = 191 × 191, and slice thickness = 0.5 mm.
Fig. 1a and 1b clearly show the gradual decrease of PL intensity and red-shift of the emission along with the increase of the Mn2+ doping ratio for all the QDs with a shell growth time of 5 h. The PLQY decreased from an initial 25.2% for undoped QDs to 18.9% for a doping ratio of 9.9%. Nevertheless, this fluorescence quantum yield still ranks at the top of those for aqueously prepared Cd-free QDs at similar emission wavelengths (∼780 nm),46–49 as shown in Table S2.† It should also be mentioned that the decrease of PL intensity caused by the Mn2+ dopant is relatively not significant compared with those cases for doping magnetic ions into QD cores,50,51 suggesting the important role of the ZnS shell as a spacer between the underlying ZCISe core and the dopant to boost the PLQY. The observed red-shift of the emission peak wavelength from 750 nm to 778 nm after successful Mn2+ doping is consistent with previous reports, which can be attributed to the interaction between the 3d electrons of Mn2+ and charge carriers in the conduction/valence band.52 Moreover, the doping did not change the nature of broad excitation (400–700 nm) and excitation-independent emission of ZCISe@ZnS QDs as shown in Fig. 1c and Fig. S2,† providing great flexibility in the choice of excitation light sources for practical applications.
To understand the Mn2+ doping effects on the photoluminescence process, the charge carrier recombination kinetics of doped QDs as a function of the Mn2+ doping level was further studied by time-resolve PL measurements. The PL decay curves determined at their corresponding PL peak wavelengths are shown in Fig. 1d. In general, all QDs have PL relaxations characterized by multiexponential decay processes. Their best fits were obtained by three exponential functions, which are summarized in Table S3.† The calculated average PL lifetimes are generally long (>250 ns). For the Mn-doped QDs, it is obvious that the average lifetimes show a strong dependence on the Mn2+ doping levels. Along with the increase in the Mn2+ doping ratio, the average lifetime exhibits a sharp decline from the initial 319 ns and then gradually decreases to 256 ns as shown in the upper panel of Fig. 1e. The apparently lowered lifetime is mainly caused by the acceleration of the slowest decay channel (from initial 490 ns for undoped QDs to 394 ns for 9.9% of the Mn2+ doping level), while the recombination rates of the other two channels remain nearly unchanged. The slowest decay channel is largely related to the donor–acceptor pair (DAP) recombination,25,27 which finds support from the emission wavelength-dependent PL lifetime of the QDs with a Mn2+ doping ratio of 9.9% (Fig. 1f and Table S4†), and this dependence was also observed for undoped QDs (Fig. S3 and Table S5†). In principle, the introduction of dopants into the QD lattice could inevitably create new Mn2+-related defects, especially considering that Mn2+ doping started simultaneously with ZnS shell coating across the core/shell interfaces. In this case, the doped Mn2+ ions could affect the charge carrier recombination process through newly formed defect states associated with interfacial Mn2+ dopants in the ZnS shell, leading to the decreased PLQY value, as evidenced by an apparent increase of the non-radiative recombination rate as a function of the Mn2+ doping level (the lower panel of Fig. 1e).
In order to study the effects of Mn2+ doping on the structure of ZCISe@ZnS QDs, TEM analysis combined with XRD was carried out. As shown in Fig. 2a–c, the morphology and monodispersity of the QDs exhibit no obvious change after 9.9% of Mn2+ doping, with an average particle size of about 3.0 nm. The XRD patterns of all QDs in Fig. 2d match well with the tetragonal crystal phase of CuInSe2 QDs (JCPDS card no. 40-1487), which are consistent with the HRTEM results shown in the insets of Fig. 2a and 2b. In particular, for Mn-doped QDs, the diffraction peaks at about 44° show a slight shift towards a larger angle. This might be due to that the interdiffusion of Zn2+ and Mn2+ ions to the core of the QDs results in the lattice shrinkage,51 since the ion radii of Zn2+ (74 pm) and Mn2+ (70 pm) were smaller than those of In3+ (80 pm) and Cu+ (77 pm).53 These results further demonstrate the successful doping of the Mn element into ZCISe@ZnS QDs.
XPS was performed to identify the valence state of the Mn element in the QDs, and Fig. 2e clearly displays the characteristic peak of the Mn 2p3/2 signal appearing at 641.6 eV, demonstrating that the dopants are in the Mn(II) state. The results shown in Fig. S4† also confirm the gradual incorporation of the Mn element into the QDs and the valence state of Cu within the QDs to be Cu(I). The EPR spectra for QDs of increasing Mn2+ doping levels are given in Fig. 2f, which were characterized by a six-line hyperfine splitting pattern appearing for all the levels of Mn2+ doping (with the g value in a range of 2.003–2.007). In contrast, only a background signal was observed for undoped QDs. The six-line patterns belong to the signature of the electron-nuclear hyperfine coupling of Mn2+ (nuclear spin I = 5/2).54 The EPR results demonstrate that Mn2+ ions were successfully incorporated into the ZnS shell. Compared with broad EPR resonances without splitting reported for Mn-doped CuIn(S,Se)2-based QDs,25,52 which may be due to the formation of manganese clusters, the current results are more consistent with the case for CdSe/Zn1−xMnxS nanoparticles, where Mn2+ ions tend to be doped homogeneously into the ZnS shell lattice by facilely substituting Zn2+.54,55 Furthermore, the relatively high hyperfine splitting constant A values of about 90 × 10−4 cm−1 are similar to those for Mn-doped CdTe/ZnS QDs reported previously,54 indicating that the isolated Mn2+ ions appear to locate near the surface of the thin ZnS shell of the QDs.
Since the doped Mn2+ ions within the QDs can affect the MRI signals of nuclear longitudinal relaxation of water protons as paramagnetic centers, the current QDs are expected to show great potential for MRI application. In order to evaluate the capability of the doped QDs to shorten the longitudinal relaxation time (T1) and transverse relaxation time (T2) of water protons, the relaxivities of the QDs with a Mn2+ doping level of 9.9% were determined using a 7.0 T MRI scanner as described in the Experimental section in detail. As shown in Fig. 3c and 3d, the QDs show significant T1 and T2 MR contrast enhancement effects, with a remarkable increase of concentration-dependent longitudinal relaxation rate (1/T1) and transverse relaxation rate (1/T2). Through linear fitting, the molar longitudinal relaxivity r1 and transverse relaxivity r2 can be extracted to be 4.7 and 57.6 mM−1 s−1, respectively. According to the origin of T1 enhancement, the longitudinal relaxivity of water protons involved in the inner sphere can be enhanced by slowing the tumbling of the paramagnetic Mn2+ dopants distributed near the shell surface.54,56 Surprisingly, the transverse relaxivity of water protons was also increased simultaneously by Mn-doped QDs, integrating dual T1 and T2 contrast enhancements into one QD. Such optimization of the relaxometric properties favors the rational design of multiparametric MRI contrast agents.
In addition to the above magnetic properties, in order to evaluate the generation ability of reactive oxygen species (ROS) from the Mn-doped QDs, EPR measurements were conducted to distinguish the possible ROS qualitatively. Here, 100 μM of H2O2 was used for EPR tests to simulate those existing within the tumor microenvironment. As shown in Fig. 3e and 3f, both 1O2 and ·OH were largely generated in the presence of Mn-doped QDs and light irradiation (638 nm for 10 min, 0.72 W cm−2). In contrast, the lack of irradiation only yielded quite limited ·OH, suggesting that the current QDs have the potential to kill tumor cells through the generation of excessive ROS when activated by light.
Next, the fluorescence imaging capability and photodynamic efficacy of ZCISe@ZnS:Mn QDs were evaluated on MCF-7 cells. The cells incubated with free Mn2+ ions and ZCISe@ZnS QDs were used as control groups. As shown in Fig. 4a, the confocal fluorescence microscopy images acquired under a red channel (560–800 nm) reveal that the cells treated with the QDs show a strong red fluorescence signal of QDs, while those incubated with free Mn2+ ions exhibit nearly no fluorescence signal under the same conditions. This result suggests that the current QDs can be ingested by cancer cells. Since the Mn2+ doping did not largely lower the PLQY of the QDs, the fluorescence signal intensities of the cells show no distinct difference for doped and undoped QDs. In particular, upon 638 nm light irradiation for 5 min, the fluorescence signals of cancer cells show no obvious decline, manifesting the high stability of the QDs.
For visualizing the intracellular ROS, all cells were treated with DCFH-DA before imaging under a green channel (525–560 nm). As shown in the third row of Fig. 4a, fluorescence signals can be observed for the cells treated with free Mn2+ ions, indicating that Mn2+ ions can convert a certain amount of endogenous H2O2 into ROS through Fenton-like reactions inside the cells, which is similar to the case for applying the Fenton-like activity of Mn2+ ions to generate ·OH from H2O2.57,58 In contrast, the cells treated with PBS show no fluorescence signal (Fig. S5†). The undoped QDs also led to a certain degree of green fluorescence, which may be attributed to the radicals transformed from the photoexcited charge carriers during the non-radiative recombination processes of ZCISe@ZnS QDs. Interestingly, for the Mn-doped QDs, the fluorescence of the cells is significantly enhanced, largely due to the synergistic effect of the Fenton-like activity of doped Mn2+ ions distributed near the surface of the thin ZnS shell and photodynamic process of the QDs for boosting the production of ROS. To prove whether light irradiation can enhance the above two pathways, the cells were further treated with the same three samples under 638 nm light irradiation for 5 min. Free Mn2+ ions show no apparent enhancement of the ROS yield, suggesting that the Fenton-like activity of free Mn2+ ions did not change much under the current irradiation conditions. The fluorescence signals caused by the undoped QDs show an obvious increase because light irradiation can give rise to more radicals through non-radiative relaxations. Quite excitingly, the cells treated with the Mn-doped QDs exhibit further enhanced fluorescence after light irradiation, demonstrating that light can promote both the nonradiative recombination of the QD core and doped Mn2+ ion-associated Fenton-like reactions and thus yield more ROS. This might involve photo-assisted Fenton reactions as previously reported for a Cu2−xSe nanoparticle-based system for effectively producing ROS.59 Overall, the Mn-doped ZCISe@ZnS QDs can combine chemodynamic and photodynamic processes for effectively yielding ROS to achieve great potential for killing cancer cells.
To assess the photodynamic efficacy in vitro, the viabilities of MCF-7 cells after being treated with ZCISe@ZnS:Mn QDs of different concentrations were studied. Calcein-AM and PI co-stainings were adopted to distinguish live and dead cells. As shown in Fig. 4b, the Mn-doped QDs under irradiation at 638 nm (0.72 W cm−2 for 10 min) resulted in a gradual increase of dead cells (red) when the QD concentration reached above 0.5 μM, and most cells were killed by the QDs with a concentration up to 5 μM in the presence of light irradiation. In contrast, the number of dead cells treated with the QDs without laser irradiation is far smaller. Therefore, ZCISe@ZnS:Mn QDs can efficiently kill MCF-7 cells upon light irradiation, showing favorable properties for photodynamic therapy.
As a proof of concept, four different fluorescence channels, i.e., λex 500/λem 780, λex 500/λem 820, λex 605/λem 780, and λex 605/λem 820, were selected to jointly image the solid tumors. Before the in vivo experiment, the multi-channel imaging performance of the QD solution was first evaluated on the imaging equipment. As presented in Fig. 5b, the multi-channel fluorescence images of QD PBS solutions in the Eppendorf tube were acquired. The QD solution shows strong fluorescence signals in all four channels but with different intensities. Specifically, QDs can be excited by both 500 nm and 605 nm lasers to emit bright NIR light peaked at the wavelengths of 780 nm and 820 nm respectively, which exhibited the strongest fluorescence in the λex 605/λem 780 channel. This optical performance of QD solution in different fluorescence channels can also be confirmed by the quantitative analysis of fluorescence intensity values, as shown in Fig. 5c. These data imply that the current QDs possess the potential to detect tumors in vivo through all these fluorescence channels.
To confirm this expectation, a mouse bearing subcutaneous tumor was adopted to validate the tumor-specific imaging performance of the QDs in vivo. The PBS solution of the QDs with a dose of 2.45 mg Cu per kg body weight was intravenously administered into the mouse through its caudal vein. The fluorescence images of the right hind leg of the mouse were acquired before and at different time points after the injection of the QDs. As shown in Fig. 5d, after the QDs were delivered intravenously, the NIR fluorescence signals at the tumor site became apparent 10 min after injection. Thereafter, the signals of the tumor region quickly increased in intensity and reached a maximum at approximately 30 min post-injection in all fluorescence channels, suggesting that the QDs are stable in a physiological environment and can specifically accumulate in the tumor tissue, allowing the multi-channel diagnosis of the tumors in vivo. Through the quantitative analysis of the fluorescence signal intensities derived from tumor and the surrounding tissues, the temporal evolution of the signal-to-background ratio of the tumor region exhibited a roughly similar tendency. These results indicate that although the fluorescence signal intensities of tumor vary among these four different channels, the location of solid tumor can be distinguished in all these channels, in which the tumor tissue exhibited a ∼1.5 times higher signal intensity than the surrounding tissues at 30 min post-injection (Fig. 5e).
In order to better show the tumor imaging performance of the current QDs, the line-scanning spectra drawn across the tumor region in a bright field image and a λex 605/λem 780 channel fluorescence image were obtained, as a proof of concept. As presented in Fig. 5f, the background of the curve image was set to light yellow and green to distinguish the tumor segment and the tissue segment. Interestingly, these two curves showed a symmetrical opposite trend. On one hand, owing to the angiogenesis and tissue denaturation, the skin on the grafting tumor exhibited a darker color compared with the surrounding normal skin in the gray image of the bright field, indicated by the low signal values of the tumor segment of the bright field curve. On the other hand, the tumor segment of the fluorescence curve exhibited a significant increase of the signal intensity value compared to the tissue segments on both sides, suggesting that the fluorescent signal of tumor is specifically enhanced by the QDs. In addition, the signal enhancement at the junction of tumor and tissue segments is very sharp, indicating that the tumor margin can be well identified. The symmetrically opposite trend of these two curves confirms the co-localization of enhanced fluorescence signals and tumor region. These above results indicate that the tumor region can be precisely identified by QD-based tumor imaging, with high spatial resolution.
For further validating the tumor contrast enhancement of the QDs, the relative signal intensities of tumor at pre-injection and 30 min post-injection were recorded. As shown in the upper panel of Fig. 5g, through quantitative analysis, the relative signal intensity trend of the tumor region in vivo is consistent with that of QD solution in Eppendorf tubes in four different channels as shown in Fig. 5b. However, even if the fluorescent signal intensities of tumor were distinct in different channels, the intensity ratios at 30 min post-injection to pre-injection in these imaging channels are almost identical, i.e., the tumor contrast was enhanced by ∼1.9 times after 30 min injection of QDs in all imaging channels.
To further confirm the tumor accumulation of the QDs, the main organs including the heart, liver, spleen, lung, kidney, and tumor were harvested, and subjected to ex vivo fluorescence imaging. As shown in Fig. S6,† the ex vivo tumor tissue of the mouse at the λex 605/λem 780 channel still exhibited an obvious fluorescence signal even if the fluorescence signal of tumor has been greatly faded at 4 h post-injection in the in vivo imaging, and this result supports the excellent tumor retention properties of the current QDs.
To investigate the contrast enhancement performance of the QDs in multiparametric MRI, different MRI sequences were selected to simultaneously show the brain section of the mice. The detailed procedures are given in Fig. 6a. In the clinic, T1WI and T2WI have been widely employed as the basic MRI sequences to reveal the anatomical structure of the brain. As shown in Fig. 6b and 6c, the image contrast between different encephalic regions is not obvious before the intracranial injection of the QDs, only the boundary of hippocampus is vaguely visible in T2WI. In contrast, after intracranial injection of the QDs, significant signal enhancements appeared inside the brain. Specifically, a bright signal and a dark signal can be observed around the injection needle track and injection point in T1WI and T2WI, respectively. In addition, the bright/dark signals were also distributed in the lateral ventricle at the edge of the alveus of the hippocampus, which largely enhanced the contrast of the boundary between the hippocampus and cortex, suggesting that the QDs may diffuse into the lateral ventricle through the needle track. Apparently, the signals with the same spatial distribution but opposite trends in T1WI and T2WI indicate that the QDs can simultaneously serve as positive and negative contrast agents in these two MRI sequences.
In addition to T1WI and T2WI, T2*WI and SWI, two gradient-recalled-echo sequences of MRI that have been used for detecting brain micro-bleeding in the clinic, were also adopted for brain imaging. As shown in Fig. 6d and 6e, the negative enhancement signals can be clearly observed in both T2*WI and SWI after the intracranial injection of the QDs. More importantly, the spatial distribution of the negative signals in these two MRI sequences matched well with that of the aforementioned enhanced signals in T1WI and T2WI, indicating that these negative signals are attributed to the injected QDs. These results indicate that the current QDs can serve as the multiparametric MRI contrast agents for T1WI, T2WI, T2*WI, and SWI.
In order to further evaluate the enhancement of the imaging contrast by the QDs in different MRI sequences, the signal intensities in the above MR images were quantitatively analyzed. In detail, the signal intensities of the QD accumulation regions in the mouse brain after injection and the corresponding brain regions before injection were recorded, respectively. According to the paired t-test statistics of signal intensities derived from three imaging planes of each MRI sequence (Fig. 6f–i), the average signal intensities of the QD accumulation area post-injection and the corresponding area pre-injection are statistically different (p < 0.05), indicating that the injected QDs can bring significant tissue contrast enhancement for multiparametric MRI.
Therefore, the current QDs can significantly enhance the imaging contrast of local brain tissues in vivo with different MRI sequences including T1WI, T2WI, T2*WI and SWI, realizing the contrast enhanced multiparametric MRI of the brain.
Footnote |
† Electronic supplementary information (ESI) available. See DOI: https://doi.org/10.1039/d3nr02385k |
This journal is © The Royal Society of Chemistry 2023 |